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Sugar esters display surface-active properties, wetting, emulsifying, and other physicochemical phenomena following their amphipathic nature and recognize distinct biological activity. The development of nutritional pharmaceuticals and other applications remains of great interest. Herein, three novel homologous series of several N-mono-fatty acyl amino acid glucosyl esters were synthesized, and their physicochemical properties and biological activities were evaluated. The design and preparation of these esters were chemically performed via the reaction of glucose with different fatty acyl amino acids as renewable starting materials, with the suggestion that they would acquire functional characteristics superior and competitive to certain conventional surfactants. The synthesized products are characterized using FTIR, 1H-NMR, and 13C-NMR spectroscopy. Further, their physicochemical properties, such as HLB, CMC, Γmax, γCMC, and Amin, were determined. Additionally, their antimicrobial and anticancer efficiency were assessed. The results indicate that the esters' molecular structure, including the acyl chain length and the type of amino acid, significantly influences their properties. The measured HLB ranged from 8.84 to 12.27, suggesting their use as oil/water emulsifiers, wetting, and cleansing agents. All esters demonstrate promising surface-active characteristics, with moderate to high foam production with good stability. Notably, compounds 6-O-(N-dodecanoyl, tetradecanoyl cysteine)-glucopyranose (34, 35), respectively and 6-O-(N-12-hydroxy-9-octadecenoyl cysteine)-glucopyranose (38) display superior foamability. Wetting efficiency increased with decreasing the chain length of the acyl group. The storage results reveal that increasing the fatty acyl hydrophobe length enhances the derived emulsion's stability for up to 63 days. Particularly, including cysteine in these glucosyl esters improves wetting, foaming, and emulsifying potentialities. Furthermore, the esters exhibit antibacterial activity against several tested Gram-positive and Gram-negative bacteria and fungi. On the other hand, they show significant antiproliferative effects on some liver tumor cell lines. For instance, compounds 6-O-(N-12-hydroxy-9-octadecenoylglycine)-glucopyranose (28), 6-O-(N-dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoylvaline)- glucopyranose (29, 31, 32 and 33), respectively in addition to the dodecanoyl, hexadecanoyl, 9-octadecenoyl and 12-hydroxy-9-octadecenoyl cysteine glucopyranose (34, 36, 37 and 38), respectively significantly inhibit the examined cancer cells. [ABSTRACT FROM AUTHOR]

Peroxiredoxin 6 (Prdx6) repairs peroxidized membranes by reducing oxidized phospholipids, and by replacing oxidized sn-2 fatty acyl groups through hydrolysis/reacylation by its phospholipase A 2 (aiPLA 2) and lysophosphatidylcholine acyltransferase activities. Prdx6 is highly expressed in the lung, and intact lungs and cells null for Prdx6 or with single-point mutations that inactivate either Prdx6-peroxidase or aiPLA 2 activity alone exhibit decreased viability, increased lipid peroxidation, and incomplete repair when exposed to paraquat, hyperoxia, or organic peroxides. Ferroptosis is form of cell death driven by the accumulation of phospholipid hydroperoxides. We studied the role of Prdx6 as a ferroptosis suppressor in the lung. We first compared the expression Prdx6 and glutathione peroxidase 4 (GPx4) and visualized Prdx6 and GPx4 within the lung. Lung Prdx6 mRNA levels were five times higher than GPx4 levels. Both Prdx6 and GPx4 localized to epithelial and endothelial cells. Prdx6 knockout or knockdown sensitized lung endothelial cells to erastin-induced ferroptosis. Cells with genetic inactivation of either aiPLA 2 or Prdx6-peroxidase were more sensitive to ferroptosis than WT cells, but less sensitive than KO cells. We then conducted RNA-seq analyses in Prdx6-depleted cells to further explore how the loss of Prdx6 sensitizes lung endothelial cells to ferroptosis. Prdx6 KD upregulated transcriptional signatures associated with selenoamino acid metabolism and mitochondrial function. Accordingly, Prdx6 deficiency blunted mitochondrial function and increased GPx4 abundance whereas GPx4 KD had the opposite effect on Prdx6. Moreover, we detected Prdx6 and GPx4 interactions in intact cells, suggesting that both enzymes cooperate to suppress lipid peroxidation. Notably, Prdx6-depleted cells remained sensitive to erastin-induced ferroptosis despite the compensatory increase in GPx4. These results show that Prdx6 suppresses ferroptosis in lung endothelial cells and that both aiPLA 2 and Prdx6-peroxidase contribute to this effect. These results also show that Prdx6 supports mitochondrial function and modulates several coordinated cytoprotective pathways in the pulmonary endothelium. [Display omitted] • Ferroptosis is a form of cell death driven by the accumulation of phospholipid hydroperoxides. • Prdx6 limits lipid peroxidation in the lung via its peroxidase, PLA 2 , and LPCAT activities. • Prdx6 KO, KD, or KI pulmonary cells without Prdx6-peroxidase or PLA 2 are sensitized to ferroptosis. • Prdx6 deficiency blunts mitochondrial function and upregulates GPx4, which interacts with Prdx6. • Prdx6 is a cytoprotective protein that guards the pulmonary endothelium against ferroptosis. [ABSTRACT FROM AUTHOR]

Latent tuberculosis, caused by dormant Mycobacterium tuberculosis (Mtb), poses a threat to global health through the incubation of undiagnosed infections within the community. Dormant Mtb, which is phenotypically tolerant to antibiotics, accumulates triacylglycerol (TAG) utilizing fatty acids obtained from macrophage lipid droplets. TAG is vital to mycobacteria, serving as a cell envelope component and energy reservoir during latency. TAG synthesis occurs by sequential acylation of glycerol‐3‐phosphate, wherein the second acylation step is catalyzed by acylglycerol‐3‐phosphate acyltransferase (AGPAT), resulting in the production of phosphatidic acid (PA), a precursor for the synthesis of TAG and various phospholipids. Here, we have characterized a putative acyltransferase of Mtb encoded by Rv3816c. We found that Rv3816c has all four characteristic motifs of AGPAT, exists as a membrane‐bound enzyme, and functions as 1‐acylglycerol‐3‐phosphate acyltransferase. The enzyme could transfer the acyl group to acylglycerol‐3‐phosphate (LPA) from monounsaturated fatty acyl‐coenzyme A of chain length 16 or 18 to produce PA. Complementation of Escherichia coli PlsC mutant in vivo by Rv3816c confirmed that it functions as AGPAT. Its active site mutants, H43A and D48A, were incapable of transferring the acyl group to LPA in vitro and were not able to rescue the growth defect of E. coli PlsC mutant in vivo. Identifying Rv3816c as AGPAT and comparing its properties with other AGPAT homologs is not only a step toward understanding the TAG biosynthesis in mycobacteria but has the potential to explore it as a drug target. [ABSTRACT FROM AUTHOR]

An important mechanism of gene expression regulation is the epigenetic modification of histones. The cofactors and substrates for these modifications are often intermediary metabolites, and it is becoming increasingly clear that the metabolic and nutritional state of cells can influence these marks. These connections between the balance of metabolites, histone modifications and downstream transcriptional changes comprise a metabolic signaling program that can enable cells to adapt to changes in nutrient availability. Beyond acetylation, there is evidence now that histones can be modified by other acyl groups. In this Cell Science at a Glance article and the accompanying poster, we focus on these histone acylation modifications and provide an overview of the players that govern these acylations and their connections with metabolism. [ABSTRACT FROM AUTHOR]

This article presents a method for synthesizing N-containing polycyclic compounds through a radical annulation cyclization reaction. The authors demonstrate the versatility of this method by synthesizing a range of tetrahydro-6H-indeno[2,1-c]quinolinone derivatives. The article also provides background information on acylation reactions and their importance in synthetic organic chemistry and pharmaceutical development. The given text is a list of references to scientific articles covering various topics in organic chemistry and catalysis, which can be valuable resources for researchers in the field. [Extracted from the article]

Mulberry leaf is a widely used protein feed and is often used as a strategy to reduce feed costs and improve meat quality in the livestock industry. However, to date, there is a lack of research on the improvement of meat quality using mulberry leaves, and the exact mechanisms are not yet known. The results showed that fermented mulberry leaves significantly reduced backfat content but had no significant effect on intramuscular fat (IMF). Lipidomic analysis showed that 98 and 303 differential lipid molecules (p < 0.05) were identified in adipose and muscle tissues, respectively, including triglycerides (TG), phosphatidylcholine, phosphatidylethanolamine, sphingolipids, and especially TG; therefore, we analysed the acyl carbon atom number of TG. The statistical results of acyl with different carbon atom numbers of TG in adipose tissue showed that the acyl group containing 13 carbon atoms (C13) in TG was significantly upregulated, whereas C15, C16, C17, and C23 were significantly downregulated, whereas in muscle tissue, the C12, C19, C23, C25, and C26 in TG were significantly downregulated. Acyl changes in TG were different for different numbers of carbon atoms in different tissues. We found that the correlations of C (14–18) in adipose tissue were higher, but in muscle tissue, the correlations of C (18–26) were higher. Through pathway enrichment analysis, we identified six and four metabolic pathways with the highest contributions of differential lipid metabolites in adipose and muscle tissues respectively. These findings suggest that fermented mulberry leaves improve meat quality mainly by inhibiting TG deposition by downregulating medium‐ and short‐chain fatty acids in backfat tissue and long‐chain fatty acids in muscle tissue. [ABSTRACT FROM AUTHOR]

Covering: up to 2023 Specialized metabolite (SM) modifications and/or decorations, corresponding to the addition or removal of functional groups (e.g. hydroxyl, methyl, glycosyl or acyl group) to SM structures, contribute to the huge diversity of structures, activities and functions of seed and plant SMs. This review summarizes available knowledge (up to 2023) on SM modifications in Brassicaceae and their contribution to SM plasticity. We give a comprehensive overview on enzymes involved in the addition or removal of these functional groups. Brassicaceae, including model (Arabidopsis thaliana) and crop (Brassica napus, Camelina sativa) plant species, present a large diversity of plant and seed SMs, which makes them valuable models to study SM modifications. In this review, particular attention is given to the environmental plasticity of SM and relative modification and/or decoration enzymes. Furthermore, a spotlight is given to SMs and related modification enzymes in seeds of Brassicaceae species. Seeds constitute a large reservoir of beneficial SMs and are one of the most important dietary sources, providing more than half of the world's intake of dietary proteins, oil and starch. The seed tissue- and stage-specific expressions of A. thaliana genes involved in SM modification are presented and discussed in the context of available literature. Given the major role in plant phytochemistry, biology and ecology, SM modifications constitute a subject of study contributing to the research and development in agroecology, pharmaceutical, cosmetics and food industrial sectors. [ABSTRACT FROM AUTHOR]

This article, published in Chemistry of Natural Compounds, explores the use of fungi to produce fine chemicals through whole cell cultures. The researchers specifically focus on the transformation of the fertility agent Dydrogesterone (DYD) using the fungus Aspergillus flavus. They provide spectroscopic data for the compounds formed during this transformation and conduct antimicrobial bioassays. The article highlights the potential of fungi in modifying steroidal and non-steroidal compounds and suggests the need for further research in this area. The study found that A. flavus was able to transform DYD into various products, and the antifungal activity of these products was tested against different fungi and bacteria. The document also provides details on the experimental methods used in the study. [Extracted from the article]

In this article, we report a very efficient method for the determination of the enantiopurity of 1,2-diacyl-sn-glycero-3-phosphocholine by 1H NMR analysis using a readily available chiral derivatizing boronic acid (CDA), (R)-(2-(((1-phenylethyl)amino)methyl)phenyl)boronic acid. After the removal of the acyl groups of 1,2-diacyl-sn-glycero-3-phosphocholine via methanolysis and washing fatty acid byproducts with CHCl3, the obtained sn-glycero-3-phosphocholine (GPC) with the free diol moiety is derivatized by the chiral boronic acid and analyzed by 1H NMR analysis. The choline methyl resonance of each diastereomer is observed at distinctive chemical shifts in the 1H NMR spectrum. Integration of the respective resonances allows direct determination of the enantiomeric purity. The procedure was tested successfully using 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) with different enantiomeric purities and with commercially available 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). [ABSTRACT FROM AUTHOR]

Sirt2 is a nicotinamide adenine dinucleotide (NAD+)- dependent protein lysine deacylase that can remove both acetyl group and long- chain fatty acyl groups from lysine residues of many proteins. It was reported to affect inflammatory bowel disease (IBD) symptoms in a mouse model. However, conflicting roles were reported, with genetic knockout aggravating while pharmacological inhibition alleviating IBD symptoms. These seemingly conflicting reports cause confusion and deter further efforts in developing Sirt2 inhibitors as a potential treatment strategy for IBD. We investigated these conflicting reports and elucidated the role of Sirt2 in the mouse model of IBD. We essentially replicated these conflicting results and confirmed that Sirt2 inhibitors' protective effect is not through off- targets as two very different Sirt2 inhibitors (TM and AGK2) showed similar protection in the IBD mouse model. We believe that the differential effects of inhibitors and knockout are due to the fact that the Sirt2 inhibitors only inhibit some but not all the activities of Sirt2. This hypothesis is confirmed by the observation that a PROTAC degrader of Sirt2 did not protect mice in the IBD model, similar to Sirt2 knockout. Our study provides an interesting example where genetic knockout and pharmacological inhibition do not align and emphasizes the importance of developing substrate- dependent inhibitors. Importantly, we showed that the effect of Sirt2 inhibition in IBD is through regulating the gut epithelium barrier by inhibiting Arf6- mediated endocytosis of E- cadherin, a protein important for the intestinal epithelial integrity. This mechanistic understanding further supports Sirt2 as a promising therapeutic target for treating IBD. [ABSTRACT FROM AUTHOR]

Amides are important intermediates in organic chemistry and the pharmaceutical industry, but their low reactivity requires catalysts and/or severe reaction conditions for esterification. Here, a novel approach was devised to convert amides into esters without the use of transition metals. The method effectively overcomes the inherent low reactivity of amides by employing dimethylsulfate-mediated reaction to activate the C-N bonds. To confirm the proposed reaction mechanism, control experiments and density functional theory (DFT) calculations were conducted. The method demonstrates a wide array of substrates, including amides with typical H/alkyl/aryl substitutions, N,N-disubstituted amides, amides derived from alkyl, aryl, or vinyl carboxylic acids, and even amino acid substrates with stereocentres. Furthermore, we have shown the effectiveness of dimethylsulfate in removing acyl protective groups in amino derivatives. This study presents a method that offers efficiency and cost-effectiveness in broadening the esterification capabilities of amides, thereby facilitating their increased utilization as synthetic compounds in diverse transformations. Amides are important intermediates in organic chemistry and the pharmaceutical industry, but their low reactivity requires catalysts and/or harsh reaction conditions to esterify them. Here, the authors report a versatile and mild dimethyl sulfate-mediated reaction to activate and esterify C—N bonds, achieving up to 95% amide bond cleavage. [ABSTRACT FROM AUTHOR]

The number of β-arylamino-2-oxy-5-methylpropiophenones has been synthesized by reacting of β- dimethylamino-2-oxy-5-methylpropiophenone hydrochloric acid salt with aniline derivatives in order to use these compounds as stabilizers for polyethylene. It was shown that the thermal stability of the compounds, depending on the nature of the substituent in the aniline fragment of the molecule was observed in a temperature range between 165 and 213°C. All studied compounds, introduced into polyethylene, increased its resistance to temperature effects. It was revealed that β-arylamino-2-oxy-5-methylpropiophenones had a stabilizing effect due to the suppression of thermo-oxidative degradation of polyethylene. They multiplied the oxidation induction period of polyethylene and reduced the rate of oxidation. Among the compounds studied β-phenoxybenzylamino-2-oxy-5-methylpropiophenone showed the highest stabilizing effect. All studied compounds had sufficient light-stabilizing activity, substantially due the presence in their molecules of a strong intramolecular hydrogen bond IHB (OH ... O = C) of the chelate type between the phenolic hydroxyl proton and the carbonyl oxygen of the acyl group. [ABSTRACT FROM AUTHOR]

The 2H‐tetrahydro‐4,6‐dioxo‐1,2‐oxazine (TDO) ring, a rare structural motif embedded in the molecular architecture of alchivemycins, is synthesized from 2,2,6‐trimethyl‐4H‐1,3‐dioxin‐4‐one via two routes. Both routes involve the intramolecular trapping of an acylketene intermediate by an internal hydroxy group to form the TDO ring as a key step. The first synthesis was achieved in 29 % overall yield from the starting material by a four‐step sequence featuring a DMAP−CaCl2‐mediated O‐ to C‐acyl migration reaction to install an acyl group at the C5 position of the TDO ring. The second synthesis was completed in 8 % overall yield from the same starting material as the first one through five steps by exploiting a photo‐induced double bromination reaction. [ABSTRACT FROM AUTHOR]

Lipids represent a large group of biomolecules that are responsible for various functions in organisms. Diseases such as diabetes, chronic inflammation, neurological disorders, or neurodegenerative and cardiovascular diseases can be caused by lipid imbalance. Due to the different stereochemical properties and composition of fatty acyl groups of molecules in most lipid classes, quantification of lipids and development of lipidomic analytical techniques are problematic. Identification of different lipid species from complex matrices is difficult, and therefore individual analytical steps, which include extraction, separation, and detection of lipids, must be chosen properly. This review critically documents recent strategies for lipid analysis from sample pretreatment to instrumental analysis and data interpretation published in the last five years (2019 to 2023). The advantages and disadvantages of various extraction methods are covered. The instrumental analysis step comprises methods for lipid identification and quantification. Mass spectrometry (MS) is the most used technique in lipid analysis, which can be performed by direct infusion MS approach or in combination with suitable separation techniques such as liquid chromatography or gas chromatography. Special attention is also given to the correct evaluation and interpretation of the data obtained from the lipid analyses. Only accurate, precise, robust and reliable analytical strategies are able to bring complex and useful lipidomic information, which may contribute to clarification of some diseases at the molecular level, and may be used as putative biomarkers and/or therapeutic targets. [ABSTRACT FROM AUTHOR]

Mucor circinelloides lipase Lip10 is a dual-functional enzyme with lipolytic activity and phospholipid:diacylglycerol acyltransferase (PDAT) activity in aqueous phase. However, the catalytic properties of Lip10 and its structural characteristics remain unknown. The present study systematically investigated its PDAT activity and lipolytic activity using six phospholipid substrates, 18:0 triacylglycerol and 16:0 1,2-diacylglycerol, predict the 3D structure of Lip10 using AlphaFold2, and evaluated residues' flexibility through molecular dynamics analysis. Lip10 exhibited a preference for phosphorylethanolamine (PE) with a long-chain fatty acyl group and showed the lipolytic activity to 18:0 triacylglycerol and 16:0 1.2-diacylglycerol. 20 mM Mg2+ and Fe2+ can significantly increase the PDAT activity of Lip10 by 50–80%. Molecular docking analysis suggest that the lower binding energy for 18:0 PE with Lip10 contributes to the higher structural stability of the complex of 18:0 PE and Lip10. Mutations of Phe565Asp and Glu318Met increase PDAT activity of Lip10 by 3.6-fold and 2.7-fold, while the TAG content produced by mutants Lip10Phe103Pro, Lip10Ile487Lys and Lip10Phe570Asp decrease by 33%− 43%. The present study demonstrated structural properties of the dual-functional lipase Lip10 and provide a theoretical basis to study its roles in the lipid metabolism of M. circinelloides in the future. [Display omitted] • Lip10 is a dual-functional enzyme with lipolytic activity and PDAT activity in aqueous phase. • Lip10 exhibited stronger PDAT activity when 18:0 PE was used as the substrate. • Lip10 showed the lipolytic activity to 18:0 triacylglycerol and 16:0 1.2-diacylglycerol. • Mutations of Phe565Asp and Glu318Met increase PDAT activity of Lip10 by 3.6-fold and 2.7-fold. • TAG produced by mutants Lip10Phe103Pro, Lip10Ile487Lys and Lip10Phe570Asp decrease by 33%− 43%. [ABSTRACT FROM AUTHOR]

Since the discovery of the sirtuin family founding member (i.e., the yeast silent information regulator 2 (sir2) protein) in 2000, more and more sirtuin proteins have been identified and are currently known to be present in organisms from all the three kingdoms of life (i.e., bacteria, archaea, and eukarya). Seven sirtuin proteins have been identified in mammals including humans, that is, SIRT1/2/3/4/5/6/7. Sirtuin proteins are a class of enzymes with primary catalytic activity being the β‐nicotinamide adenine dinucleotide (β‐NAD+ or NAD+)‐dependent deacylation from the Nε‐acyl‐lysine residues on cellular proteins. Many sirtuins (e.g., human SIRT1/2/3/4/5/6/7) have been found to each possess multiple individual deacylase activities acting on Nε‐acyl‐lysine substrates with different acyl groups ranging from the simple formyl and acetyl to the more complex groups like succinyl and myristoyl; however, our current knowledge on the (patho)physiological roles of these individual deacylase activities is still limited, which could be due to the currently still thin research toolbox for investigation (i.e., the deacylase‐selective sirtuin mutant and inhibitor/activator). In this article, an updated account on the subject matter will be presented with biochemical and medicinal chemistry perspectives. [ABSTRACT FROM AUTHOR]

Protein lipidation plays critical roles in regulating protein function and localization. However, the chemical diversity and specificity of fatty acyl group utilization have not been investigated using untargeted approaches, and it is unclear to what extent structures and biosynthetic origins of S-acyl moieties differ from N-and O-fatty acylation. Here, we show that fatty acylation patterns in Caenorhabditis elegans differ markedly between different amino acid residues. Hydroxylamine capture revealed predominant cysteine S-acylation with 15-methylhexadecanoic acid (isoC17:0), a monomethyl branched-chain fatty acid (mmBCFA) derived from endogenous leucine catabolism. In contrast, enzymatic protein hydrolysis showed that N-terminal glycine was acylated almost exclusively with straight-chain myristic acid, whereas lysine was acylated preferentially with two different mmBCFAs and serine was acylated promiscuously with a broad range of fatty acids, including eicosapentaenoic acid. Global profiling of fatty acylated proteins using a set of click chemistry-capable alkyne probes for branched-and straight-chain fatty acids uncovered 1,013 S-acylated proteins and 510 hydroxylamine-resistant N-or O-acylated proteins. Subsets of S-acylated proteins were labeled almost exclusively by either a branched-chain or a straight-chain probe, demonstrating acylation specificity at the protein level. Acylation specificity was confirmed for selected examples, including the S-acyltransferase DHHC-10. Last, homology searches for the identified acylated proteins revealed a high degree of conservation of acylation site patterns across metazoa. Our results show that protein fatty acylation patterns integrate distinct branches of lipid metabolism in a residue-and protein-specific manner, providing a basis for mechanistic studies at both the amino acid and protein levels. [ABSTRACT FROM AUTHOR]

We developed intramolecular carboxyamidations of alkyne‐tethered O‐acylhydroxamates followed by either thermally induced spontaneous or 4‐(dimethylamino)pyridine‐catalyzed O→O or O→N acyl group migration. Under iron‐catalyzed conditions, the carboxyamidation products were generated in high yield from both Z‐alkene and arene‐tethered substrates. DFT calculations indicate that the iron‐catalyzed carboxyamidation proceeds via a stepwise mechanism involving iron‐imidyl radical cyclization followed by intramolecular acyloxy transfer from the iron center to the alkenyl radical center to furnish the cis‐carboxyamidation product. Upon treatment with 4‐(dimethylamino)pyridine, the Z‐alkene‐tethered carboxyamidation products underwent selective O→O acyl migration to generate 2‐acyloxy‐5‐acyl pyrroles. Thermal O→N acyl migration occurs during carboxyamidation if the Z‐alkene linker contains an alkyl or an aryl substituent at the β‐position of the carbonyl group. On the other hand, the arene linker‐containing compounds selectively undergo O→N acyl migration to generate N‐acyl‐3‐acylisoindolinones, and the corresponding O→O acyl migration forming isoindole derivatives was not observed. [ABSTRACT FROM AUTHOR]

Protein post-translational modifications (PTMs) with various acyl groups play central roles in Streptomyces. But whether these acyl groups can be further modified, and the influences of these potential modifications on bacterial physiology have not been addressed. Here in Streptomyces roseosporus with rich crotonylation, a luciferase monooxygenase LimB is identified to elaborately regulate the crotonylation level, morphological development and antibiotic production by oxidation on the crotonyl groups of an acetyl-CoA synthetase Acs. This chemical modification on crotonylation leads to Acs degradation via the protease ClpP1/2 pathway and lowered intracellular crotonyl-CoA pool. Thus, we show that acyl groups after PTMs can be further modified, herein named post-PTM modification (PPM), and LimB is a PTM modifier to control the substrate protein turnover for cell development of Streptomyces. These findings expand our understanding of the complexity of chemical modifications on proteins for physiological regulation, and also suggest that PPM would be widespread. Protein crotonylation, as one of post-translational modifications (PTMs), can be further modified, herein named post-PTM (PPM) by a monooxygenase in Streptomyces to regulate substrate protein turnover and cell physiology. [ABSTRACT FROM AUTHOR]

A selective reaction of bridged ozonides with Fe(II) salts proceeds through the sequence of O−O, C−C scissions and halogenation to form α‐halogen substituted δ‐ketoesters and δ‐diketones in 15–72% yields. The overall sequence shows how a temporary installation of a peroxide functionality can be used to replace the acyl group within an acetoacetic ester unit with a halogen. [ABSTRACT FROM AUTHOR]

Euglobals are a subclass of acylphloroglucinols, mostly found in plants of the Eucalyptus genus. They possess anticancer activity, being potent inhibitors of the Epstein–Barr virus activation. Their molecules can be viewed as acylphloroglucinol monoterpene or sesquiterpene adducts, with the former having greater activity than the latter. The acylphloroglucinol moiety contains two mutually meta acyl (R–C=O) groups, respectively, in ortho and meta positions with respect to the two C atoms shared by the two moieties. The current work focuses on euglobal molecules in which R = H is in one acyl group and R = isobutyl is in the other. It aims to identify the property differences between molecules having the same terpene moiety and the two acyl groups in reversed positions. Ten such pairs were studied computationally using different levels of theory (HF, DFT, and MP2). The results highlight considerable differences between the two molecules of each pair, regarding molecular features such as relative energies, characteristics of the intramolecular hydrogen bonds (IHBs), dipole moment, bond vibrational frequencies, and frequency changes caused by the IHBs. A comparison of the results from the different levels of theory utilised shows similar patterns for the influence of position reversal on the same characteristic. [ABSTRACT FROM AUTHOR]

Sirtuins (SIRT) are unique posttranslational modification enzymes that utilize NAD + as co-substrate to remove acyl groups from lysine residues. SIRT act on variety of substrates and impact major metabolic process. All seven members of SIRT family are unique and targets wide range of cellular proteins in nucleus, cytoplasm, and mitochondria for post-translational modification by acetylation (SIRT1, 2, 3, and 5) or ADP-ribosylation (SIRT4 and 6). Each member of SIRT family is distinct. SIRT2 was first to be discovered that incited research on mammalian SIRT. Enzymatic activities of SIRT 4 are yet to be elucidated while only SIRT7 is localized in nucleoli that govern the transcription of RNA polymerase I. SIRT 5 and 6 exhibit weakest deacetylase activity. Out of all SIRT analogs, SIRT1 is identified as nutrient sensor. Increased expression of only SIRT3 is linked with longevity in humans. Since SIRT is regulated by the bioenergetic state of the cell, nutrition impacts it but very few studies about diet-mediated effect on SIRT are reported. The present review elaborates distribution, specific biological role and prominent effect of all SIRT on vital human tissue along with highlighting need to trace molecular mechanisms and identifying foods that may augment it beneficially. [ABSTRACT FROM AUTHOR]

Chemical modification of starch from the chayote root (Sechium edule Jacq) is carried out with lauric acid and acetic anhydride. The modified starch is characterized by Fourier‐transform infrared spectrometry (FTIR), X‐ray diffraction (XRD), and Differential Scanning Calorimetry (DSC) and used to formulate edible films. The developed edible films are characterized based on their physicochemical and mechanical properties. The physicochemical and functional properties of starch are affected by the incorporation of the acyl and acetyl group. Both starches exhibit a significant decrease in solubility. Starch modified by the incorporation of the acyl group (lauroyl) has higher thermal stability than starch modified by the incorporation of the acetyl group. The first shows an increase in emulsifying and foaming capacity, as well as water‐ and oil‐retention capacity, while the second exhibits adequate edible film‐forming properties. The edible films develop with modified starch with acetyl group has a homogeneous surface and exhibit a higher percentage of elongation at break when they are stored at a water activity of 0.561. In accordance with the above, it is concluded that the chayote root starch modified has physicochemical and functional properties that indicate their potential utility in the food industry. [ABSTRACT FROM AUTHOR]

The kinetics of nucleophilic substitution reactions involving 2,4‐dinitrophenyl 5‐substituted‐2‐thiophenecarboxylate were studied kinetically with 4‐Z‐C6H4O−/4‐Z‐C6H4OH, which facilitated the reactions, in 20 mol% DMSO(aq). The reactions followed second‐order kinetics and exhibited βacyl = −2.34 to −2.92, ρ(Y) = 2.71–3.39, βnuc = 0.74–0.83, and |βlg| = 0.40–0.57. Based on the interpretation of the results, we have concluded that the reaction follows an addition–elimination mechanism in which the first step is the rate‐determining step (rds). The transition state structures for the 4‐ZC6H4O−‐promoted reactions remained nearly the same with a change in the leaving group from 4‐nitrophenoxide to 2,4‐dinitrophenoxide. The mechanism of the 4‐ZC6H4O−‐promoted reaction was similar to that of R2NH‐promoted reactions, except that the former proceeded with the 1st step being the rds and the latter proceeded with a change in the rds from the second to the first step with a stronger nucleophile. [ABSTRACT FROM AUTHOR]

A single acyloxy group at C‐2 can control the outcome of nucleophilic substitution reactions of pyran‐derived acetals, but the extent of the neighboring‐group participation depends on a number of factors. We show here that neighboring‐group participation does not necessarily control the stereochemical outcome of acetal substitution reactions with weak nucleophiles. The 1,2‐trans selectivity increased with increasing reactivity of the incoming nucleophile. This trend suggests the intermediacy of both cis‐fused dioxolenium ions and oxocarbenium ions in the stereochemistry‐determining step. In addition, as the electron‐donating ability of the neighboring group decreased, the preference for the 1,2‐trans products increased. Computational studies show how the barriers for the ring‐opening reaction on the dioxolenium ions and the transition states to provide the oxocarbenium ions change with the electron‐donating capacity of the C‐2‐acyloxy group and the reactivity of the nucleophile. [ABSTRACT FROM AUTHOR]

Isoquinolones and isoquinolines are crucial natural and synthetic heterocyclic compounds exhibiting a range of biological activities. A less explored strategy for the recyclization of isocoumarins to isoquinolones involves the transformation of 1H‐isochromen‐1‐ones with a carbonyl group at position 3 using primary amines. This study presents a straightforward one‐pot protocol for the recyclization of 3‐acetyl‐ and 3‐benzoylisocoumarins into their corresponding isoquinolone derivatives using structurally diverse primary amines. This provides versatile and scalable routes for accessing a variety of 2‐R‐isoquinolin‐1(2H)‐ones. Interestingly, the acyl group also reacted with the hydroxyl group of 2‐aminoethanol, leading to the simultaneous formation of 3,4‐dihydro[1,4]oxazino[4,3‐b]isoquinolin‐6(1H)‐ones alongside lactone recyclization. Moreover, the recyclization process was accompanied by more complex alternative cyclizations, including an oxidative‐reductive stage. For instance, the recyclization of isocoumarins with benzylamine resulted in the formation of isochromeno[3,4‐c]pyrroles, whereas with glycine derivatives, 1,2‐dihydro‐6H‐pyrazino[1,2‐b]isoquinolin‐3,6(4H)‐diones were obtained. [ABSTRACT FROM AUTHOR]

Given the important role of carboxylesterase 2 (CES2) in the metabolism of various esters, it is of significance to develop a tool to determine endogenous CES2 activity in a rapid and highly selective manner. In this work, an "off-on" rhodamine-based fluorescent probe is reported as an effective tool for CES2 activity. Based on the substrate recognition preference of CES2 (large alcohol and small acyl groups), the probe with dimethyl carbamate as the recognition group performs well in terms of selectivity and sensitivity to CES2. The fluorescence switching control of the probe for CES2 was achieved by using the spirolactone structure of rhodamine. The probe shows the fast generation of a fluorescence signal at 634 nm upon hydrolysis of CES2 with excitation at 578 nm. The results showed a linear relationship between the fluorescence intensity at 634 nm and the CES2 activity from 0 to 4 μg/mL. The probe reacts rapidly with CES2, and the reaction is stable within 40 minutes. The probe is highly selective for CES2, with a detection limit as low as 0.303 μg/mL. In addition, the probe has currently been successfully utilized to evaluate CES2 activity in living cells. Hence, this probe is anticipated to be significant in identifying endogenous CES2 activity in intricate biological settings. [ABSTRACT FROM AUTHOR]

Cardiolipin and phosphatidylinositol along with the latter’s phosphorylated derivative phosphoinositides, control a wide range of cellular functions from signal transduction, membrane traffic, mitochondrial function, cytoskeletal dynamics, and cell metabolism. An emerging dimension to these lipids is the specificity of their fatty acyl chains that is remarkably distinct from that of other glycerophospholipids. Cardiolipin and phosphatidylinositol undergo acyl remodeling involving the sequential actions of phospholipase A to hydrolyze acyl chains and key acyltransferases that re-acylate with specific acyl groups. LCLAT1 (also known as LYCAT, AGPAT8, LPLAT6, or ALCAT1) is an acyltransferase that contributes to specific acyl profiles for phosphatidylinositol, phosphoinositides, and cardiolipin. As such, perturbations of LCLAT1 lead to alterations in cardiolipin-dependent phenomena such as mitochondrial respiration and dynamics and phosphoinositide-dependent processes such as endocytic membrane traffic and receptor signaling. Here we examine the biochemical and cellular actions of LCLAT1, as well as the contribution of this acyltransferase to the development and specific diseases. [ABSTRACT FROM AUTHOR]

Naturally occurring benzophenones represent a relatively small group of plant metabolites with narrow distribution, mainly in members of Clusiaceae, Gentianaceae, Hypericaceae, Polygalaceae, Myrtaceae, etc.; however, there were reports of several compounds derived from microorganisms belonging to the Aspergillaceae and Valsaceae families and propolis. Benzophenones exhibit many biological activities, such as antioxidant, anti-inflammatory, cytotoxic, antimicrobial, etc. Few reviews on benzophenones that have appeared in the literature were focused on their prenylated derivatives. Summarized information on structural diversity, distribution, and biological activities of simple oxygenated naturally occurring benzophenones and their glycosides has not been found in the literature. Until 2000, only benzophenone C-glycosides were known to occur in nature. Since then, many O-glycosides have been isolated, structurally, and biologically characterized. This review covers the years from 1850 to 2023 and was compiled using databases such as Chemical Abstracts, Scopus, Google Scholar, PubMed, and ResearchGate. Based on their degree of oxidation, 210 chemical structures of benzophenone derivatives and glycosides were grouped into six categories. In addition, in one group of 40 miscellaneous benzophenones, where one or several protons are replaced by a methyl, alcohol, carboxyl, or acyl group, glycosidic forms with such an aglycone and dimeric compounds with xanthone was included. Simple oxygenated benzophenones and their glycosides were found in 77 plant genera belonging to 44 families. The allergy-associated bezophenone-1, benzophenone-2 and benzophenone-3 have limited distribution across natural sources. A wide range of biological activities (antioxidant, anti-inflammatory, cytotoxic, antitumor, cytoprotective, antimicrobial, MAO-A, antiarthritic, anticholinesterase, anti-atherosclerotic, laxative, etc.) of simple oxygenated benzophenones and their glycosides that appeared in the literature were discussed. [ABSTRACT FROM AUTHOR]

The covalent modification of bacterial (lipo)polysaccharides with discrete substituents may impact their biosynthesis, export and/or biological activity. Whether mycobacteria use a similar strategy to control the biogenesis of its cell envelope polysaccharides and modulate their interaction with the host during infection is unknown despite the report of a number of tailoring substituents modifying the structure of these glycans. Here, we show that discrete succinyl substituents strategically positioned on Mycobacterium tuberculosis (Mtb) lipoarabinomannan govern the mannose-capping of this lipoglycan and, thus, much of the biological activity of the entire molecule. We further show that the absence of succinyl substituents on the two main cell envelope glycans of Mtb, arabinogalactan and lipoarabinomannan, leads to a significant increase of pro-inflammatory cytokines and chemokines in infected murine and human macrophages. Collectively, our results validate polysaccharide succinylation as a critical mechanism by which Mtb controls inflammation. Author summary: Mycobacterium tuberculosis, the agent of tuberculosis (TB) in humans, remains the leading cause of death due to a single infectious agent. In the context of the increasing incidence of multidrug-resistant TB infections, understanding the key physiological processes allowing this paramount pathogen to adapt and thrive in the stressful environment of the host may prove useful in designing innovative therapeutic strategies. The covalent modifications of cell envelope (lipo)polysaccharides with discrete substitutions such as (amino)sugars, amino acids, phosphates or acyl groups is a well-established strategy used by a variety of bacteria to enhance virulence and resistance to antibiotics and host defense mechanisms. While increasing evidence points to M. tuberculosis similarly fine-tuning the structure of its glycans with various tailoring substituents, their biological significance remains essentially unknown. We here show that the succinylation of the dominant cell envelope polysaccharides of M. tuberculosis governs their decoration with additional, biologically active, glycosyl substituents and promotes the establishment of infection by controlling inflammation. [ABSTRACT FROM AUTHOR]

A novel fluorescent probe based on azamonardine (Aza) fluorophore was designed and synthesized for the highly selective detection of cysteine (Cys) in vivo and in vitro. After reacting with acryloyl chloride, the fluorescence of Aza is effectively quenched, resulting in the formation of the Aza-acryl probe. Upon the addition of Cys, the ester bond of Aza-acryl is cleaved, releasing a new compound (Compound 1) with strong fluorescence, thereby achieving fluorescence turn-on detection of Cys. The structure of Aza-acryl was characterized using X-ray crystallography and NMR spectroscopy. Additionally, density functional theory was employed to elucidate the quenching mechanism of the acyl group on the Aza. Aza-acryl exhibits high selectivity towards Cys and distinguishes it from other biothiols such as homocysteine (Hcy) and glutathione (GSH). The mechanism of Aza-acryl for detecting Cys was investigated through HPLC, NMR spectroscopy, high-resolution mass spectrometry, and reaction kinetics experiments. Aza-acryl demonstrates excellent imaging capabilities for Cys in cells and zebrafish, providing a reliable and selectable tool for the detection and imaging of Cys in biological systems. [ABSTRACT FROM AUTHOR]

Cardiac function is a dynamic process that must adjust efficiently to the immediate demands of physical state and activity. So too, the metabolic support of cardiac function is a dynamic process that must respond, in time, to the demands of cardiac function and viability. Flux through metabolic pathways provides chemical energy and generates signaling molecules that regulate activity among intracellular compartments to meet these demands. Thus, flux through metabolic pathways provides a dynamic mode of support of cardiomyocytes during physiological and pathophysiological challenges. Any inability of metabolic flux to keep pace with the demands of the cardiomyocyte results in progressive dysfunction that contributes to cardiac disease. Thus, the priority in maintaining and regulating flux through metabolic pathways in the cardiomyocyte cannot be understated. Great potential exists in current efforts to elucidate metabolic mechanisms as therapeutic targets for the diseased heart. As a consequence, detecting metabolic flux in the functioning myocardium of the heart, under normal and diseased conditions, is essential in elucidating the metabolic basis of contractile dysfunction. As a companion to the 2022 ISHR Research Achievement Award lecture, this review examines the use and applications of stable isotope kinetics to quantify metabolic flux through intermediary pathways and the exchange and transport of intermediates across the mitochondrial membrane and sarcolemma of intact functioning hearts in determining how these intracellular events are coordinated to support cardiac function and health. Finally, this work reviews recently demonstrated metabolic defects in diseased hearts and the potential for metabolic alleviation of heart disease. A glimpse inside cardiomyocyte metabolism within the beating heart via dynamic-mode 13C NMR spectroscopy reveals mechanisms coordinating pathophysiological state with metabolic flux. Delivery of carbon-13 (13C) enriched substates to the heart enable NMR-based detection (Middle panel showing sequential NMR spectra) of tricarboxylic acid (TCA) cycle and malate-aspartate (M/A) shuttle fluxes through progressive labeling of carbon positions within glutamate (GLU) (Top right panel, least squares fitting of metabolite pool content to enrichment at glutamate C-4 and C-3 carbons), as well as turnover of long chain fatty acids (LCFA) (blue squares) and initial exponential entry phase (red dotted line) within the triglyceride (TG) pool and (Bottom right panel) in the lipid droplets. End-point in vitro NMR of acetyl CoA enrichment and mass spectrometry of 13C and 12C enrichment of acyl groups in TG in sampled myocardium, enables measurement of total flux. Kinetic analysis of resulting isotopic enrichment curves coupled with end-point measures of metabolite pool size and 13C enrichment yield quantitative flux values in response to cardiac function and pathophysiological state. [Display omitted] [ABSTRACT FROM AUTHOR]

Synthesis of bicyclic scaffolds has attracted tremendous attention because they are playing an important role as saturated bioisosteres of benzenoids in modern drug discovery. Here, we report a BF3‐catalyzed [2π+2σ] cycloaddition of aldehydes with bicyclo[1.1.0]butanes (BCBs) to access polysubstituted 2‐oxabicyclo[2.1.1]hexanes. A new kind of BCB containing an acyl pyrazole group was invented, which not only significantly facilitates the reactions, but can also serve as a handle for diverse downstream transformations. Furthermore, aryl and vinyl epoxides can also be utilized as substrates which undergo cycloaddition with BCBs after in situ rearrangement to aldehydes. We anticipate that our results will promote access to challenging sp3‐rich bicyclic frameworks and the exploration of BCB‐based cycloaddition chemistry. [ABSTRACT FROM AUTHOR]

Acyl group migration has been the subject of several studies. Such migration processes may cause problems during synthesis, isolation, and purification of different acyl‐bearing compounds, and have biological relevance, for example, in the metabolism of pharmaceuticals. Considering the recent evidence of acyl group migration being possible even over glycosidic bonds, it could be hypothesized to be involved also in the regulation of biological activity of natural polysaccharides in the host cells. Migrations are mostly observed in carbohydrates, typically having several hydroxyl groups near each other. Several studies have investigated the migration in a single or only a few different carbohydrate molecules, providing different suggestions for the mechanisms of migration, seldom supported by comprehensive computational investigations. In this concept article we discuss the recent progress on the mechanistic aspects of acyl group migration, with carbohydrates in particular focus. [ABSTRACT FROM AUTHOR]

A new benzyl-type protecting group (1,4-dimethoxynaphthalene-2-methyl, 'DIMON') for hydroxyl functions can be selectively removed under oxidative conditions without damaging polyunsaturated fatty acyl groups. Its application is shown by the first synthesis of an ether (plasmanyl) phospholipid containing the docosa-(4Z,7Z,10Z,13Z,16Z,19Z)-hexaenoyl group. [ABSTRACT FROM AUTHOR]

A novel gelator (named DN) was designed and synthesized with an acyl hydrazone group as the self-assembly site. It can be self-assembled into stable organogels (named ODN) in N,N-dimethylformamide (DMF) with a critical gel temperature and concentration (60 °C and 10 mg mL−1). Interestingly, under 365 nm UV light, the ODN exhibits bright blue Aggregation Induced Emission (AIE), which could respond to multiple external stimuli. The supramolecular organogel ODN shows a fluorescent "OFF" response to the metal ion Fe3+ and the state of the gel ODN remains constant before and after detection. Notably, metal gels (Fe-ODN) formed by ligating ODN gel with Fe3+ can detect H2PO4− with increased fluorescence intensity emission. When Fe3+ and H2PO4− are added alternately to the ODN, the fluorescence response cycle "ON–OFF–ON" can be performed at least four times. The binding mechanism of the supramolecular organogels (ODN) to ions has been investigated through a series of characterization experiments. Meanwhile, the organogel sensor ODN can also be used as an ion-responsive membrane for the detection of Fe3+ and H2PO4−. [ABSTRACT FROM AUTHOR]

In order to improve the thermal stability of perovskite solar cells (PSCs) and reduce production costs, hole transport layer (HTL)‐free carbon‐based CsPbI3 PSCs (C‐PSCs) have attracted the attention of researchers. However, the power conversion efficiency (PCE) of HTL‐free CsPbI3 C‐PSCs is still lower than that of PSCs with HTL/ metal electrodes. This is because the direct contact between the carbon electrode and the perovskite layer has a higher requirement on the crystal quality of perovskite layer and matched energy level at perovskite/carbon interface. Herein, the acyl chloride group and its derivative trichloroacetyl chloride are used to passivate CsPbI3 C‐PSCs for the first time. The results show that the carbonyl group of trichloroacetyl chloride can effectively passivate the uncoordinated Pb2+ ions in perovskite. At the same time, leaving group Cl− ions can increase the grain size of perovskite and improve the crystallization quality of perovskite layer. In addition, the trichloroacetyl chloride tends to generate cesium chloride acetate, which acts as an electron blocking layer, reduces charge recombination, promotes gradient energy level arrangement, and effectively improves the separation and extraction ability of carriers. The PCE of CsPbI3 HTL‐free C‐PSCs is successfully increased from 13.40% to 14.82%. [ABSTRACT FROM AUTHOR]

A simple method for the synthesis of cyclopropane compounds via cross‐coupling reaction between tertiary cyclopropyl carbagermatranes and acyl chlorides was reported. Derivatives of acryloyl chloride and aliphatic acyl chloride also performed to be suitable substrates. This process can be used to introduce a wide range of functionalized cyclopropane groups and acyl groups directly. [ABSTRACT FROM AUTHOR]

We developed a route to rhodomyrtone analogs that feature different acyl groups at C7. Since electrophilic substitution reactions on the aryl part of the rhodomyrtone core led to C5 derivatives, the C5 position was blocked by a chlorine. Subsequent Duff type formylation followed by Grignard addition to the aldehyde group and oxidation gave various phenones. The benzyl protecting groups were removed by hydrogenation or boron tribromide. Some derivatives turned out to be quite active against multiple resistant Staphylococcus aureus strains and a rhodomyrtone resistant mutant (RomR). The chlorine at C5 seems to have a beneficial effect on the antibacterial activity. [ABSTRACT FROM AUTHOR]

"Through space" palladium/hydrogen shift is an efficient strategy to achieve selective functionalization of a specific remote C−H bond. Compared with relatively extensive exploited 1,4‐palladium migration process, the relevant 1,5‐Pd/H shift was far less investigated. We herein report a novel 1,5‐Pd/H shift pattern between a vinyl and an acyl group. Through the pattern, rapid access to 5‐membered‐dihydrobenzofuran and indoline derivatives has been achieved. Further studies have unveiled an unprecedented trifunctionalization (vinylation, alkynylation and amination) of a phenyl ring through 1,5‐palladium migration relayed decarbonylative Catellani type reaction. A series of mechanistic investigations and DFT calculations have provided insights into the reaction pathway. Notably, it was unveiled that the 1,5‐palladium migration in our case prefers a stepwise mechanism involving a PdIV intermediate. [ABSTRACT FROM AUTHOR]

"Through space" palladium/hydrogen shift is an efficient strategy to achieve selective functionalization of a specific remote C−H bond. Compared with relatively extensive exploited 1,4‐palladium migration process, the relevant 1,5‐Pd/H shift was far less investigated. We herein report a novel 1,5‐Pd/H shift pattern between a vinyl and an acyl group. Through the pattern, rapid access to 5‐membered‐dihydrobenzofuran and indoline derivatives has been achieved. Further studies have unveiled an unprecedented trifunctionalization (vinylation, alkynylation and amination) of a phenyl ring through 1,5‐palladium migration relayed decarbonylative Catellani type reaction. A series of mechanistic investigations and DFT calculations have provided insights into the reaction pathway. Notably, it was unveiled that the 1,5‐palladium migration in our case prefers a stepwise mechanism involving a PdIV intermediate. [ABSTRACT FROM AUTHOR]

The difunctionalization of unsaturated compounds offers great advantages regarding step- and atom-economy for the construction of various vicinal functional groups. Introducing acyl and trifluoromethylthio groups into compounds simultaneously still remains a challenge. Using S-trifluoromethyl thioesters as bifunctional reagents, we developed photoredox/copper dual-catalyzed 1,2-acyl-trifluoromethylthiolation of alkenes and 1,4-acyl-trifluoromethylthiolation of 1,3-enynes. β-Trifluoromethylthiolated ketones and δ-trifluoromethylthiolated β-allenyl ketones can be obtained in moderate to good yields with broad functional group compatibility. More broadly, by combining S-trifluoromethyl thioesters with other radical precursors, trifluoromethylthio-fluoroalkylation and trifluoromethylthio-arylation of alkenes could be realized, respectively. [ABSTRACT FROM AUTHOR]

Multiblock copolymers are envisioned as promising materials with enhanced properties and functionality compared with their diblock/triblock counterparts. However, the current approaches can construct multiblock copolymers with a limited number of blocks but tedious procedures. Here, we report a thioester‐relayed in‐chain cascade copolymerization strategy for the easy preparation of multiblock copolymers with on‐demand blocks, in which thioester groups with on‐demand numbers are built in the polymer backbone by controlled/living polymerizations. These thioester groups further serve as the in‐chain initiating centers to trigger the acyl group transfer ring‐opening polymerization of episulfides independently and concurrently to extend the polymer backbone into multiblock structures. The compositions, number of blocks, and block degree of polymerization can be easily regulated. This strategy can offer easy access to a library of multiblock copolymers with ≈100 blocks in only 2 to 4 steps. [ABSTRACT FROM AUTHOR]

Multiblock copolymers are envisioned as promising materials with enhanced properties and functionality compared with their diblock/triblock counterparts. However, the current approaches can construct multiblock copolymers with a limited number of blocks but tedious procedures. Here, we report a thioester‐relayed in‐chain cascade copolymerization strategy for the easy preparation of multiblock copolymers with on‐demand blocks, in which thioester groups with on‐demand numbers are built in the polymer backbone by controlled/living polymerizations. These thioester groups further serve as the in‐chain initiating centers to trigger the acyl group transfer ring‐opening polymerization of episulfides independently and concurrently to extend the polymer backbone into multiblock structures. The compositions, number of blocks, and block degree of polymerization can be easily regulated. This strategy can offer easy access to a library of multiblock copolymers with ≈100 blocks in only 2 to 4 steps. [ABSTRACT FROM AUTHOR]

Glyceryl monostearate is extensively used as an emulsifier in many industries. Mono acylation of glycerol was carried out by utilizing immobilized Candida antarctica lipase B (Cal B) as a biocatalyst and vinyl stearate as an acyl donor. Different reaction parameters, such as selection of lipases from various sources (like Candida antarctica, Candida rugosa, and Mucor meihei) and their quantity, shaking speed, temperature, substrate concentration, and reusability were studied in detail to achieve excellent conversion. Overall, 98% conversion of glycerol was obtained at a mole ratio of 1:1 of glycerol to vinyl stearate, using 12 mg of immobilized Cal B at 45 °C for 3 h. The mechanism of the given reaction was anticipated based on the results of the Lineweaver-Burk plots. It was found that the reaction followed the Ping-Pong Bi Bi mechanism with inhibition of glycerol. As it was a kinetically controlled synthesis, different kinetic constants were estimated by non-linear regression analysis. The activation energy for Cal B was found to be 10.3 kcal/mol. Further, biocatalyst can be reused up to four catalytic cycles with an average four percent loss of activity. A molecular docking study was done to find out the confirmation of substrates and their binding positions in an enzyme. It was noticed that the reaction proceeds through acyl-enzyme complex formation followed by the transfer of that acyl group to another substrate. [ABSTRACT FROM AUTHOR]

Polyketides are a class of natural products with astonishing structural diversities, fascinating biological activities, and a versatile of applications. In polyketides biosynthesis, acyltransferases (ATs) are the 'gatekeeping' enzymes selecting the specific CoA-activated acyl groups as building blocks and transferring them onto the phosphopantetheine arm of acyl carrier proteins (ACPs) to enable the following condensation reactions to assemble the polyketide chain. Herein, the Art2 protein from aurantinins, a group of the antibacterial polyketides, is characterized in vitro as an AT that can load a CoA-activated succinyl unit onto the first ACP domain of Art17 (ACPArt17-1). In addition, another two proteins, GbnB and EtnB, involved in the biosynthesis of gladiolin and etnangien respectively, were traced by literature mining, homologous searching, and product structure analysis and then identified as functional succinyl-CoA ATs by the ACPArt17-1 assays. Taken together, by the assay method employing ACPArt17-1 as an acyl acceptor, we identified three ATs that can introduce a succinyl unit into the polyketide assembly line, which enriches the toolbox of polyketide biosynthetic enzymes and sets a stage for incorporating a succinyl unit into polyketide backbones in synthetic biological manners. Key points: • Three acyltransferases that are able to load ACP with a succinyl unit were characterized in vitro. • ACPArt17-1 can be used as an acceptor to assay succinyl-CoA AT from different polyketides. • The succinyl unit can be incorporated into polyketides assembly process. [ABSTRACT FROM AUTHOR]

Lysine Nɛ-acylations, such as acetylation or succinylation, are post-translational modifications that regulate protein function. In mitochondria, lysine acylation is predominantly non-enzymatic, and only a specific subset of the proteome is acylated. Coenzyme A (CoA) can act as an acyl group carrier via a thioester bond, but what controls the acylation of mitochondrial lysines remains poorly understood. Using published datasets, here we found that proteins with a CoA-binding site are more likely to be acetylated, succinylated, and glutarylated. Using computational modeling, we show that lysine residues near the CoA-binding pocket are highly acylated compared to those farther away. We hypothesized that acyl-CoA binding enhances acylation of nearby lysine residues. To test this hypothesis, we co-incubated enoyl-CoA hydratase short chain 1 (ECHS1), a CoA-binding mitochondrial protein, with succinyl-CoA and CoA. Using mass spectrometry, we found that succinyl-CoA induced widespread lysine succinylation and that CoA competitively inhibited ECHS1 succinylation. CoA-induced inhibition at a particular lysine site correlated inversely with the distance between that lysine and the CoA-binding pocket. Our study indicated that CoA acts as a competitive inhibitor of ECHS1 succinylation by binding to the CoA-binding pocket. Together, this suggests that proximal acylation at CoA-binding sites is a primary mechanism for lysine acylation in the mitochondria. [ABSTRACT FROM AUTHOR]

A photochemical cyclization of F‐tagged, o‐alkynylated N‐alkylamides to indoles catalyzed by [Ir(dF(CF3)ppy)2(dtbpy)]PF6 is presented. This straightforward and efficient reaction involves an intramolecular rearrangement due to the presence of an electron withdrawing group in the acyl moiety and is the first example of photochemically induced 1,3‐acyl shift in the cyclization towards 3‐acylindoles. A four‐step reaction sequence including the photoreaction as a key step to the desired indoles has been developed and optimized. The compatibility of differently substituted F‐tagged precursors with the photocyclization step was investigated and the robustness of this step towards modifications could be shown. In total, 16 so far unknown derivatives with diverse modifications in positions N1 and C2, bearing a pentadecafluorooctanoyl moiety as F‐tag, were synthesized in very good yields and fully characterized. [ABSTRACT FROM AUTHOR]

Taxol is a clinically used drug for the treatment of various types of cancers. Its 6/8/6/4‐membered ring (ABCD‐ring) system is substituted by eight oxygen functional groups and flanked by four acyl groups, including a β‐amino acid side chain. Here we report a 34‐step total synthesis of this unusually oxygenated and intricately fused structure. Inter‐ and intramolecular radical coupling reactions connected the A‐ and C‐ring fragments and cyclized the B‐ring, respectively. Functional groups of the A‐ and C‐rings were then efficiently decorated by employing newly developed chemo‐, regio‐, and stereoselective reactions. Finally, construction of the D‐ring and conjugation with the β‐amino acid delivered taxol. The powerful coupling reactions and functional group manipulations implemented in the present synthesis provide new valuable information for designing multistep target‐oriented syntheses of diverse bioactive natural products. [ABSTRACT FROM AUTHOR]